Maria Ciofani | Scholars@Duke

Maria Ciofani
Associate Professor of Immunology

Transcriptional Regulation of Proinflammatory Lymphocytes

IL-17-expressing CD4 T helper (Th17) cells are important members of the intestinal immune cell community that contribute to protection against bacterial and fungal infections, and maintenance of intestinal homeostasis. Although central to immunity, dysregulted Th17 cell function has been implicated in tissue inflammation and autoimmune disease (e.g. Inflammatory bowel disease, arthritis, and multiple sclerosis). In order to understand this balance between healthy and pathogenic responses, we are interested in defining the transcriptional regulatory mechanisms that govern (1) Th17 cell specification from naive T cell precursors and, (2) Th17 cell effector plasticity during inflammation. Combining genome-wide interrogation of regulatory information (transcription factor occupancy, chromatin accessibility, and transcriptional output) with gene-deficiency models in mice, we can dissect the contribution of key transcriptional regulators in proinflammatory T cell function.

We currently have open positions for students, postdoctoral fellows and a research technician.

Current Appointments & Affiliations

Associate Professor of Immunology, Immunology, Basic Science Departments 2020
Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2013

Contact Information

128 Jones Bldg, 207 Researchr, 3010 DUMC, Durham, NC 27710
maria.ciofani@duke.edu (919) 684-1166

Background
Education, Training, & Certifications
- Ph.D., University of Toronto (Canada) 2007
Duke Appointment History
- Assistant Professor of Immunology, Immunology, Basic Science Departments 2013 - 2020
Recognition
In the News
- OCT 1, 2014
  
  Maria Ciofani: Solving the Immune System’s Identity Crisis
Expertise
Subject Headings
Research
Selected Grants
- Basic Immunology Training Program awarded by National Institutes of Health 2020 - 2025
- Transplant Infectious Diseases Interdisciplinary Research Training Grant (TIDIRTG) awarded by National Institutes of Health 2018 - 2023
- Regulation of the type 1 program during ILC3 plasticity awarded by National Institutes of Health 2020 - 2022
- Molecular Mycology and Pathogenesis Training Program awarded by National Institutes of Health 2019 - 2021
- Regulatory Mechanisms of CD4+ T Cell Differentiation awarded by National Institutes of Health 2017 - 2021
- The role of AP-1 family transcription factor networks in regulating Th17 cell effector identity awarded by National Institutes of Health 2016 - 2021
- Organization and Function of Cellular Structure awarded by National Institutes of Health 1975 - 2020
- Network approach to dissecting genetic mediators of Multiple Sclerosis awarded by National Multiple Sclerosis Society 2015 - 2019
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Xu-Vanpala, Shengjie, M Elizabeth Deerhake, Joshua D. Wheaton, Morgan E. Parker, Praveen R. Juvvadi, Nancie MacIver, Maria Ciofani, and Mari L. Shinohara. “Functional heterogeneity of alveolar macrophage population based on expression of CXCL2.” Sci Immunol 5, no. 50 (August 7, 2020). https://doi.org/10.1126/sciimmunol.aba7350.
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  - Ciofani, Maria. “Tγδ17 cells build up the nerve.” Nat Immunol 21, no. 4 (April 2020): 367–68. https://doi.org/10.1038/s41590-020-0642-4.
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  - Parker, Morgan E., Alejandro Barrera, Joshua D. Wheaton, Matthew K. Zuberbuehler, David S. J. Allan, James R. Carlyle, Timothy E. Reddy, and Maria Ciofani. “c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program.” J Exp Med 217, no. 1 (January 6, 2020). https://doi.org/10.1084/jem.20191030.
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  - Espinosa, Jaclyn R., Joshua D. Wheaton, and Maria Ciofani. “In Vitro Differentiation of CD4+ T Cell Effector and Regulatory Subsets.” Methods Mol Biol 2111 (2020): 79–89. https://doi.org/10.1007/978-1-0716-0266-9_7.
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  - Parker, Morgan E., and Maria Ciofani. “Regulation of γδ T Cell Effector Diversification in the Thymus.” Front Immunol 11 (2020): 42. https://doi.org/10.3389/fimmu.2020.00042.
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  - Wheaton, Joshua D., and Maria Ciofani. “JunB Controls Intestinal Effector Programs in Regulatory T Cells.” Frontiers in Immunology 11 (January 2020): 444. https://doi.org/10.3389/fimmu.2020.00444.
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  - Juvvadi, Praveen R., David Fox, Benjamin G. Bobay, Michael J. Hoy, Sophie M. C. Gobeil, Ronald A. Venters, Zanetta Chang, et al. “Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.” Nat Commun 10, no. 1 (September 19, 2019): 4275. https://doi.org/10.1038/s41467-019-12199-1.
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  - Wheaton, Joshua, and Maria Ciofani. “JunB controls intestinal effector programs in regulatory T cells,” September 16, 2019. https://doi.org/10.1101/772194.
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  - Zuberbuehler, Matthew K., Morgan E. Parker, Joshua D. Wheaton, Jaclyn R. Espinosa, Harmony R. Salzler, Eunchong Park, and Maria Ciofani. “Publisher Correction: The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.” Nat Immunol 20, no. 5 (May 2019): 663. https://doi.org/10.1038/s41590-019-0349-6.
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  - Miraldi, Emily R., Maria Pokrovskii, Aaron Watters, Dayanne M. Castro, Nicholas De Veaux, Jason A. Hall, June-Yong Lee, et al. “Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.” Genome Res 29, no. 3 (March 2019): 449–63. https://doi.org/10.1101/gr.238253.118.
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  - Zuberbuehler, Matthew K., Morgan E. Parker, Joshua D. Wheaton, Jaclyn R. Espinosa, Harmony R. Salzler, Eunchong Park, and Maria Ciofani. “The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.” Nat Immunol 20, no. 1 (January 2019): 73–85. https://doi.org/10.1038/s41590-018-0274-0.
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  - Wheaton, Joshua D., Chen-Hao Yeh, and Maria Ciofani. “Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes.” J Immunol 199, no. 12 (December 15, 2017): 3931–36. https://doi.org/10.4049/jimmunol.1701134.
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  - Carr, Tiffany M., Joshua D. Wheaton, Geoffrey M. Houtz, and Maria Ciofani. “JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation.” Nat Commun 8, no. 1 (August 21, 2017): 301. https://doi.org/10.1038/s41467-017-00380-3.
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  - Glasmacher, Elke, Smita Agrawal, Abraham B. Chang, Theresa L. Murphy, Wenwen Zeng, Bryan Vander Lugt, Aly A. Khan, et al. “A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.” Science 338, no. 6109 (November 16, 2012): 975–80. https://doi.org/10.1126/science.1228309.
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  - Ciofani, Maria, Aviv Madar, Carolina Galan, Maclean Sellars, Kieran Mace, Florencia Pauli, Ashish Agarwal, et al. “A validated regulatory network for Th17 cell specification.” Cell 151, no. 2 (October 12, 2012): 289–303. https://doi.org/10.1016/j.cell.2012.09.016.
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  - Dervovic, Dzana D., Maria Ciofani, Korosh Kianizad, and Juan Carlos Zúñiga-Pflücker. “Comparative and functional evaluation of in vitro generated to ex vivo CD8 T cells.” J Immunol 189, no. 7 (October 1, 2012): 3411–20. https://doi.org/10.4049/jimmunol.1200979.
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  - Kirigin, Francis F., Kenneth Lindstedt, Maclean Sellars, Maria Ciofani, Siao Li Low, Lachlan Jones, Fiona Bell, et al. “Dynamic microRNA gene transcription and processing during T cell development.” J Immunol 188, no. 7 (April 1, 2012): 3257–67. https://doi.org/10.4049/jimmunol.1103175.
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  - Huh, Jun R., Monica W. L. Leung, Pengxiang Huang, Daniel A. Ryan, Michael R. Krout, Raghu R. V. Malapaka, Jonathan Chow, et al. “Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.” Nature 472, no. 7344 (April 28, 2011): 486–90. https://doi.org/10.1038/nature09978.
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  - Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “Determining γδ versus αß T cell development.” Nat Rev Immunol 10, no. 9 (September 2010): 657–63. https://doi.org/10.1038/nri2820.
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  - Chong, Mark M. W., Natalie Simpson, Maria Ciofani, Grace Chen, Amélie Collins, and Dan R. Littman. “Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells.” Genes Dev 24, no. 7 (April 1, 2010): 659–69. https://doi.org/10.1101/gad.1901610.
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  - Lauritsen, Jens Peter Holst, Gladys W. Wong, Sang-Yun Lee, Juliette M. Lefebvre, Maria Ciofani, Michele Rhodes, Dietmar J. Kappes, Juan Carlos Zúñiga-Pflücker, and David L. Wiest. “Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent.” Immunity 31, no. 4 (October 16, 2009): 565–75. https://doi.org/10.1016/j.immuni.2009.07.010.
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  - Koltsova, Ekaterina K., Maria Ciofani, Robert Benezra, Toru Miyazaki, Neil Clipstone, Juan Carlos Zúñiga-Pflücker, and David L. Wiest. “Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint.” J Immunol 179, no. 7 (October 1, 2007): 4694–4703. https://doi.org/10.4049/jimmunol.179.7.4694.
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  - Palomero, Teresa, Maria Luisa Sulis, Maria Cortina, Pedro J. Real, Kelly Barnes, Maria Ciofani, Esther Caparros, et al. “Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.” Nat Med 13, no. 10 (October 2007): 1203–10. https://doi.org/10.1038/nm1636.
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  - Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “The thymus as an inductive site for T lymphopoiesis.” Annu Rev Cell Dev Biol 23 (2007): 463–93. https://doi.org/10.1146/annurev.cellbio.23.090506.123547.
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  - Ciofani, Maria, Gisèle C. Knowles, David L. Wiest, Harald von Boehmer, and Juan Carlos Zúñiga-Pflücker. “Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation.” Immunity 25, no. 1 (July 2006): 105–16. https://doi.org/10.1016/j.immuni.2006.05.010.
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  - Zúñiga-Pflücker, Juan Carlos, and Maria Ciofani. “Pre-T cell receptor's clashing signals: "should I stay or should I go".” Immunity 24, no. 6 (June 2006): 669–70. https://doi.org/10.1016/j.immuni.2006.06.006.
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  - Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “A survival guide to early T cell development.” Immunol Res 34, no. 2 (2006): 117–32. https://doi.org/10.1385/IR:34:2:117.
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  - Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism.” Nat Immunol 6, no. 9 (September 2005): 881–88. https://doi.org/10.1038/ni1234.
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  - Schmitt, Thomas M., Maria Ciofani, Howard T. Petrie, and Juan Carlos Zúñiga-Pflücker. “Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions.” J Exp Med 200, no. 4 (August 16, 2004): 469–79. https://doi.org/10.1084/jem.20040394.
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  - Ciofani, Maria, Thomas M. Schmitt, Amelia Ciofani, Alison M. Michie, Nicolas Cuburu, Anne Aublin, Janet L. Maryanski, and Juan Carlos Zúñiga-Pflücker. “Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation.” J Immunol 172, no. 9 (May 1, 2004): 5230–39. https://doi.org/10.4049/jimmunol.172.9.5230.
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- Conference Papers
  - Hoy, M. J., D. Fox, J. Wheaton, M. Mutz, W. J. Steinbach, M. Ciofani, and J. Heitman. “Novel FK506 analog exhibits anti-fungal activity against Cryptococcus neoformans in vitro and in an animal model.” In Medical Mycology, 56:S139–S139. OXFORD UNIV PRESS, 2018.
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Teaching & Mentoring
Recent Courses
- IMMUNOL 735: Topics in Immunology 2020
- IMMUNOL 736: Topics in Immunology 2020
- IMMUNOL 735: Topics in Immunology 2019
- IMMUNOL 736: Topics in Immunology 2019
- IMMUNOL 735: Topics in Immunology 2018

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Education, Training, & Certifications

Duke Appointment History

In the News

Subject Headings

Selected Grants

Selected Publications

Academic Articles

Conference Papers

Recent Courses